Activation of Toll-Like Receptor 2 on Human Dendritic Cells Triggers Induction of IL-12, But Not IL-10

Sybille Thoma-Uszynski(University of California, Los Angeles), Sylvia M. Kiertscher(University of California, Los Angeles), Marîa Teresa Ochoa(University of California, Los Angeles), Deborah A. Bouis(The University of Texas Southwestern Medical Center), Michael V. Norgard(The University of Texas Southwestern Medical Center), Kensuke Miyake(Saga Medical School Hospital), Paul J. Godowski(Sunesis (United States)), Michael D. Roth(University of California, Los Angeles), Robert L. Modlin(University of California, Los Angeles)
The Journal of Immunology
October 1, 2000
Cited by 241

Abstract

Mammalian Toll-like receptors (TLRs) are required for cell activation by bacterial lipoproteins (bLP) and LPS. Stimulation of monocytes with bLP and LPS results in a TLR-dependent induction of immunomodulatory genes leading to the production of pro-inflammatory cytokines. In this paper, we compared the expression and response of TLRs on monocytes and dendritic cells (DC). TLR2, but not TLR4, was detected on peripheral blood monocytes and DC, in lymphoid tissue CD1alpha+ DC as well as on in vitro monocyte-derived DC. Upon stimulation with bLP or LPS, monocytes produced IL-12 and IL-10 at similar levels, whereas monocyte-derived DC produced comparable levels of IL-12, but little IL-10. Greater than 90% of the bLP-induced production of IL-12 was blocked by anti-TLR2 mAb. Thus, DC express TLR2 and activation of this receptor by bLP provides an innate mechanism by which microbial pathogens preferentially activate cell-mediated immunity.


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